The purpose of this study was to determine whether, in patients with type 2 diabetes and pre-existing disease of the heart and the circulatory system and/or the kidney, aliskiren at a target dose of 300 mg once daily (compared to placebo), on top of conventional treatment, reduces death and disease caused by the heart, the circulatory system and the kidney.

A Randomized, Double-blind, Placebo-controlled, Parallel Group Study to Determine Whether, in Patients With Type 2 Diabetes at High Risk for Cardiovascular and Renal Events, Aliskiren, on Top of Conventional Treatment, Reduces Cardiovascular and Renal Morbidity and Mortality

Percentage of Participants With Occurrence of Primary Composite Endpoint (Core : Active Treatment Phase) [ Time Frame: Time from randomization to the first event (Maximum 50 months) ]

Occurrence was defined as the first event of the following composite primary endpoint:

Cardiovascular (CV) death

Resuscitated sudden death

Non-fatal myocardial infarction (MI)

Non-fatal stroke

Unplanned hospitalization for heart failure (HF)

Onset of end-stage renal disease (ESRD) or death due to renal failure. Onset of ESRD was defined as initiation of dialysis, renal transplantation, or a serum creatinine concentration above 6.0 mg/dL (530 μmol/L), sustained for at least a month.

Doubling of baseline serum creatinine concentration, sustained for at least one month. To fulfill the endpoint, the serum creatinine concentration had to be above the upper limit of normal for men and women according to the central laboratory. The upper limit of normal for men is 1.20 mg/dL and for women is 0.91 mg/dL.

Percentage of Participants With Cardiovascular (CV) Death (Core: Active Treatment Phase) [ Time Frame: Time from randomization to the first event (Maximum 50 months) ]

Percentage of Participants With Resuscitated Sudden Death (Core: Active Treatment Phase) [ Time Frame: Time from randomization to the first event (Maximum 50 Months) ]

Resuscitated sudden death was adjudicated when a subject experiences sudden death or cardiac arrest and is successfully resuscitated by cardioversion, defibrillation or cardiopulmonary resuscitation with a meaningful recovery of consciousness. This definition excludes known transient losses of consciousness such as seizure or vasovagal episodes that do not reflect significant cardiac dysfunction.

Percentage of Participants With Fatal/Non-fatal Myocardial Infarction (MI) (Core: Active Treatment Phase) [ Time Frame: Time from randomization to the first event (Maximum 50 Months) ]

Percentage of Participants With Fatal/Non-fatal Stroke (Core: Active Treatment Phase) [ Time Frame: Time from randomization to the first event (Maximum 50 Months) ]

Percentage of Participants With Onset of End-stage Renal Disease (ESRD) (Core: Active Treatment Phase) [ Time Frame: Time from randomization to the first event (Maximum 50 Months) ]

ESRD is defined as initiation of dialysis, renal transplantation, or a serum creatinine concentration above 6.0 mg/dL (530 µmol per liter) or renal death

Percentage of Participants With Doubling of Baseline Serum Creatinine Concentration, Sustained for at Least One Month (Core: Active Treatment Phase) [ Time Frame: Time from randomization to the first event (Maximum 50 Months) ]

To fulfill the endpoint, the serum creatinine concentration had to be above the upper limit of normal for men and women according to the central laboratory. The upper limit of normal for men is 1.20 mg/dL and for women is 0.91 mg/dL.

Percentage of Participants With Unplanned Hospitalization for Heart Failure (Core: Active Treatment Phase) [ Time Frame: Time from randomization to the first event (Maximum 50 Months) ]

Percentage of Participants With All Cause Mortality (Core: Active Treatment Phase) [ Time Frame: Time from randomization to the first event (Maximum 50 months) ]

Percentage of Participants With Occurrence of Primary Composite Endpoint (Extension Phase) [ Time Frame: From cut-off date (20Dec2011/End of Treatment (EOT) ) to the first event after cut-off date (9 months in average) ]

Occurrence was defined as the first event of the following composite primary endpoint:

Cardiovascular (CV) death

Resuscitated sudden death

Non-fatal myocardial infarction (MI)

Non-fatal stroke

Unplanned hospitalization for heart failure (HF)

Onset of end-stage renal disease (ESRD) or death due to renal failure. Onset of ESRD was defined as initiation of dialysis, renal transplantation, or a serum creatinine concentration above 6.0 mg/dL (530 μmol/L), sustained for at least a month.

Doubling of baseline serum creatinine concentration, sustained for at least one month. To fulfill the endpoint, the serum creatinine concentration had to be above the upper limit of normal for men and women according to the central laboratory. The upper limit of normal for men is 1.20 mg/dL and for women is 0.91 mg/dL.

Percentage of Participants With Cardiovascular (CV) Death (Extension Phase) [ Time Frame: from cut-off date (20Dec2011/End of Treatment (EOT) ) to the first event after cut-off date (9 months in average) ]

Percentage of Participants With Resuscitated Sudden Death (Extension Phase) [ Time Frame: From cut-off date (20Dec2011/End of Treatment (EOT) ) to the first event after cut-off date (9 months in average) ]

Percentage of Participants With Fatal/Non-fatal Stroke (Extension Phase) [ Time Frame: From cut-off date (20Dec2011/End of Treatment (EOT) ) to the first event after cut-off date (9 months in average) ]

Percentage of Participants With Onset of End-stage Renal Disease (ESRD) (Extension Phase) [ Time Frame: From cut-off date (20Dec2011/End of Treatment (EOT) ) to the first event after cut-off date (9 months in average) ]

ESRD is defined as initiation of dialysis, renal transplantation, or a serum creatinine concentration above 6.0 mg/dL (530 µmol per liter) or renal death

Percentage of Participants Doubling of Baseline Serum Creatinine Concentration, Sustained for at Least One Month (Extension Phase) [ Time Frame: From cut-off date (20Dec2011/End of Treatment (EOT) ) to the first event after cut-off date (9 months in average) ]

To fulfill the endpoint, the serum creatinine concentration had to be above the upper limit of normal for men and women according to the central laboratory. The upper limit of normal for men is 1.20 mg/dL and for women is 0.91 mg/dL.

Percentage of Participants With Unplanned Hospitalization for Heart Failure (Extension Phase) [ Time Frame: From cut-off date (20Dec2011/End of Treatment (EOT) ) to the first event after cut-off date (9 months in average) ]

Percentage of Participants With All Cause Mortality (Extension Phase) [ Time Frame: from cut-off date (20Dec2011/End of Treatment (EOT) ) to the first event after cut-off date (9 months in average) ]

Secondary Outcome Measures:

Percentage of Participants With Occurrence of Secondary Cardiovascular Composite Endpoint (Core: Active Treatment Phase) [ Time Frame: Time from randomization to the first event (Maximum 50 months) ]

Occurrence was defined as the first event of the following secondary cardiovascular composite endpoint:

Cardiovascular (CV) death

Resuscitated sudden death

Non-fatal myocardial infarction (MI)

Non-fatal stroke

Unplanned hospitalization for heart failure (HF)

Percentage of Participants With Occurrence of Secondary Renal Composite Endpoint (Core: Active Treatment Phase) [ Time Frame: Time from randomization to the first event (Maximum 50 months) ]

Occurrence was defined as the first event of the following secondary renal composite endpoint:

Onset of end-stage renal disease (ESRD) or death due to renal failure. Onset of ESRD was defined as initiation of dialysis, renal transplantation, or a serum creatinine concentration above 6.0 mg/dL (530 μmol/L), sustained for at least a month.

Doubling of baseline serum creatinine concentration, sustained for at least one month. To fulfill the endpoint, the serum creatinine concentration had to be above the upper limit of normal for men and women according to the central laboratory.The upper limit of normal for men is 1.20 mg/dL and for women is 0.91 mg/dL.

Percentage of Participants With Occurrence of Secondary Cardiovascular Composite Endpoint (Extension Phase) [ Time Frame: From cut-off date (20Dec2011/End of Treatment (EOT) ) to the first event after cut-off date (9 months in average) ]

Occurrence was defined as the first event of the following secondary cardiovascular composite endpoint:

Cardiovascular (CV) death

Resuscitated sudden death

Non-fatal myocardial infarction (MI)

Non-fatal stroke

Unplanned hospitalization for heart failure (HF)

Percentage of Participants With Occurrence of Secondary Renal Composite Endpoint (Extension Phase) [ Time Frame: From cut-off date (20Dec2011/End of Treatment (EOT) ) to the first event after cut-off date (9 months in average) ]

Occurrence was defined as the first event of the following secondary renal composite endpoint:

Onset of end-stage renal disease (ESRD) or death due to renal failure. Onset of ESRD was defined as initiation of dialysis, renal transplantation, or a serum creatinine concentration above 6.0 mg/dL (530 μmol/L), sustained for at least a month.

Doubling of baseline serum creatinine concentration, sustained for at least one month. To fulfill the endpoint, the serum creatinine concentration had to be above the upper limit of normal for men and women according to the central laboratory. The upper limit of normal for men is 1.20 mg/dL and for women is 0.91 mg/dL.

Other Outcome Measures:

Percentage of Participants With Angioedema/Angioedema-like or Colorectal Events (Core : Active Treatment Phase) [ Time Frame: Time from randomization to the first event (Maximum 50 months) ]

AEs of special interest were reported according to a post-marketing commitment to Health Authorities and included angioedema/angioedema-like events and colorectal events/ procedures

Mean changes in eGFR from baseline to month 3 and month 6 were included for analysis. The LS Mean and Standard Error were based on an ANCOVA repeated-measure model with treatment, visit, treatment-by-visit and baseline eGFR as effect terms.

Percentage of Participants With Angioedema/Angioedema-like Events or Colorectal Events (Extension Phase) [ Time Frame: From cut-off date (20Dec2011/End of Treatment (EOT) ) to the first event after cut-off date (9 months in average) ]

AEs of special interest were reported according to a post-marketing commitment to Health Authorities and included angioedema/angioedema-like events and colorectal events/ procedures.

Patients who are treated with two renin-angiotensin-aldosterone-system-blockers

Patients with NYHA class III or IV heart failure

Known renal artery stenosis

Previous randomization into the AVOID trial (CSPP100C2201)

EXCLUSION SPECIFIC TO THE SAFETY FOLLOW-UP PERIOD:

- Aliskiren or aliskiren containing fixed combination products must not be used

Other protocol-defined inclusion/exclusion criteria applied

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Please refer to this study by its ClinicalTrials.gov identifier: NCT00549757